The long-term objective of this proposal is to identify the unknown morphology and pathophysiological functions of pulmonary sensory receptors, potentially benefiting more than 30 million patients with chronic obstructive pulmonary disease (COPD) and other pulmonary diseases in the US, including veterans. Dyspnea, bronchial inflammation, hyperreactivity, coughing, and mucus secretion occur when airway sensory receptors are activated. These are common clinical manifestations of pulmonary disorders; however, the underlying neural mechanisms remain unclear, in part because our knowledge of airway receptor morphology and sensory behavior is limited. Increasing evidence points to important roles of myelinated airway receptors in pulmonary diseases. In this application, we will test the hypothesis that vagal airway sensory units are not only transducers but also processors. Sensory units' behaviors depend on their structures. In addition, a single unit may contain homogeneous or heterogeneous types of receptors, providing varied, mixed behavior. In this application, we will address three specific aims to characterize the morphology and sensory behavior of myelinated airway receptors. 1) To identify different morphological structures of myelinated airway receptors by examing receptor morphology by immunohistochemical or neural tracing techniques combined with confocal microscopy. 2) To assign a specific receptor structure to physiologically defined classes of receptors, by first electrophysiologically characterizing each known receptor type, then tissue in the receptive field will be isolated, dissected, and immunohistochemically stained for receptor morphology. 3) To explore mechanosensor structure-function relationships and sensory integration mechansims by examining sensory behavior before and after blocking or stimulating one of the receptors in the unit. Thus, integration mechanisms of sensory units can be explored. Successful completion of these studies will provide important structure-function relationships and establish a comprehensive, objective classification system for the airway receptors. The presence of heterogenous receptors challenges the current view of the airway sensory unit. Transmission of heterogeneous information in a single unit verifies that the unit is not merely a transducer but also a processor. Our data will lay the foundation for future research and facilitate our understanding of the receptor function and their roles in pulmonary diseases and may help improve managements for cardiopulmonary patients suffering from cardiac failure, COPD, asthma, acute lung injury, and other pulmonary diseases. PUBLIC HEALTH RELEVANCE: Airway sensory receptors play important roles in cardiopulmonary diseases. Understanding their mechanisms of operation may help patient management, thus, benefitting a large number of veterans who suffer from cardiac and lung diseases, including cardiac failure, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and asthma.